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Eur J Clin Invest. 2015 Sep;45(9):925-31. doi: 10.1111/eci.12486. Epub 2015 Jul 14.

Ursodeoxycholyl Lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD.

Author information

1
Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
2
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
3
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University of Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND:

Hepatic fat accumulation with disturbed lipid homoeostasis is a hallmark of nonalcoholic fatty liver disease (NAFLD). The bile acid phospholipid conjugate Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a novel anti-inflammatory agent with hepatoprotective effects in murine high-fat-diet (HFD)-induced NAFLD. The aim of this work was to study changes in the hepatic lipidome due to UDCA-LPE.

MATERIALS AND METHODS:

High fat diet mouse model, mass spectometry, RT-PCR.

RESULTS:

Hepatic lipid extracts of HFD mice were analysed by mass spectrometry. The results determined higher levels of total, saturated, mono- and diunsaturated fatty acids (FA) in HFD mice, which were decreased by UDCA-LPE predominantly by the reducing the most abundant FA species palmitic acid and oleic acid. Unlike other FA species, levels of long-chain polyunsaturated fatty acids (LCPUFA), which are composed of arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were increased in HFD mice upon UDCA-LPE treatment, mainly due to elevated hepatic ARA pools. Analysis of hepatic phospholipids species showed a decrease in total phosphatidylcholine (PC), especially monounsaturated PC (PUFA-PC) levels in HFD mice. Loss of total PC was reversed due to UDCA-LPE by increasing hepatic PUFA-PC pools. Gene expression analysis showed that UDCA-LPE upregulated PPARα, a key transcriptional regulator of fatty acid oxidation, as well as downstream target genes CPT1α and AOX, which are crucially involved in mitochondrial and peroxisomal fatty acid oxidation.

CONCLUSION:

UDCA-LPE modulates defective fatty acid metabolism during experimental NAFLD thereby restoring altered lipid profiles in addition to its pronounced anti-inflammatory effects. Thus, UDCA-LPE may be a promising drug candidate for the management of NAFLD.

KEYWORDS:

Fatty acid composition; UDCA-LPE; non-alcoholic fatty liver disease

PMID:
26108973
DOI:
10.1111/eci.12486
[Indexed for MEDLINE]

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